Specificity and mechanism of TonB-dependent ferric catecholate uptake by Fiu
Taihao Yang, Ye Zou, Ho Leung Ng, Ashish Kumar, Salete M. Newton, Phillip E. Klebba
TL;DR
This study investigates how the E. coli protein Fiu transports iron complexes, revealing its specificity and mechanism for ferric catecholate uptake.
Contribution
The paper identifies the transport specificity and binding sites of Fiu, a TonB-dependent transporter, using biochemical and computational methods.
Findings
Fiu binds and transports FeEnt* with micromolar affinity but does not transport ferric monocatecholates.
Molecular simulations identified three external and one internal binding sites for FeEnt* in Fiu.
Alanine scanning mutagenesis showed that mutations in outer binding sites significantly reduced FeEnt* binding and transport.
Abstract
We studied the Escherichia coli outer membrane protein Fiu, a presumed transporter of monomeric ferric catecholates, by introducing Cys residues in its surface loops and modifying them with fluorescein maleimide (FM). Fiu-FM bound iron complexes of the tricatecholate siderophore enterobactin (FeEnt) and glucosylated enterobactin (FeGEnt), their dicatecholate degradation product Fe(DHBS)2 (FeEnt*), the monocatecholates dihydroxybenzoic acid (FeDHBA) and dihydroxybenzoyl serine (FeDHBS), and the siderophore antibiotics cefiderocol (FDC) and MB-1. Unlike high-affinity ligand-gated porins (LGPs), Fiu-FM had only micromolar affinity for iron complexes. Its apparent KD values for FeDHBS, FeDHBA, FeEnt*, FeEnt, FeGEnt, FeFDC, and FeMB-1 were 0.1, 0.7, 0.7, 1.0, 0.3, 0.4, and 4 μM, respectively. Despite its broad binding abilities, the transport repertoires of E. coli Fiu, as well as those of…
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Taxonomy
TopicsBacterial Genetics and Biotechnology · Drug Transport and Resistance Mechanisms · Chromium effects and bioremediation